Calcium sensing receptor activates the NLRP3 inflammasome via a chaperone-assisted degradative pathway involving Hsp70 and LC3-II.

Calcium sensing receptor (CaSR) activates the NLRP3 inflammasome with consequences on homeostatic responses. However, little is known about how this process is orchestrated. Since proteolysis of critical regulators of NLRP3 inflammasome contribute to its activation, we aimed to understand how CaSR stimulates proteolytic pathways to activate the NLRP3 inflammasome.

Calcium-sensing-receptor (CaSR) controls IL-6 secretion in metastatic breast cancer MDA-MB-231 cells by a dual mechanism revealed by agonist and inverse-agonist modulators.

IL-6 is a tightly controlled pleiotropic cytokine with hormone-like properties whose levels are frequently altered in cancer and inflammatory diseases. In highly invasive MDA-MB-231 breast cancer cells, basal activity of endogenously expressed calcium sensing receptor (CaSR) promotes IL-6 secretion. Interestingly, upon agonist stimulation, CaSR reduces IL-6 levels whereas it promotes secretion of various other cytokines and growth factors, raising intriguing questions about how CaSR signaling modulates IL-6 secretion.